rs10493565

Variant names:

• chr1-75234086-A-G
• rs10493565
• NM_001130058.2:c.753T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001130058.2(SLC44A5):​c.753T>C​(p.Ile251Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,610,428 control chromosomes in the GnomAD database, including 61,116 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6347 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54769 hom.)
• Consequence: SLC44A5 NM_001130058.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 15 publications found

Genes affected

SLC44A5 (HGNC:28524): (solute carrier family 44 member 5) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.704 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130058.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A5	NM_001130058.2	MANE Select	c.753T>C	p.Ile251Ile	synonymous	Exon 12 of 24	NP_001123530.1
	SLC44A5	NM_152697.6		c.753T>C	p.Ile251Ile	synonymous	Exon 12 of 24	NP_689910.2
	SLC44A5	NM_001320283.3		c.735T>C	p.Ile245Ile	synonymous	Exon 10 of 22	NP_001307212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A5	ENST00000370859.8	TSL:2 MANE Select	c.753T>C	p.Ile251Ile	synonymous	Exon 12 of 24	ENSP00000359896.3
	SLC44A5	ENST00000370855.5	TSL:1	c.753T>C	p.Ile251Ile	synonymous	Exon 12 of 24	ENSP00000359892.5

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42770 AN: 151842 Hom.: 6335 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.250 AC: 62615 AN: 250364 AF XY: 0.254

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.0674

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.269 AC: 392624 AN: 1458468 Hom.: 54769 Cov.: 31 AF XY: 0.270 AC XY: 195761 AN XY: 725736

African (AFR) AF: 0.366 AC: 12217 AN: 33384

American (AMR) AF: 0.171 AC: 7648 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8286 AN: 26070

East Asian (EAS) AF: 0.0668 AC: 2647 AN: 39628

South Asian (SAS) AF: 0.271 AC: 23333 AN: 86154

European-Finnish (FIN) AF: 0.271 AC: 14489 AN: 53382

Middle Eastern (MID) AF: 0.363 AC: 2089 AN: 5754

European-Non Finnish (NFE) AF: 0.276 AC: 305609 AN: 1109206

Other (OTH) AF: 0.271 AC: 16306 AN: 60274

GnomAD4 genome AF: 0.282 AC: 42831 AN: 151960 Hom.: 6347 Cov.: 32 AF XY: 0.279 AC XY: 20723 AN XY: 74282

African (AFR) AF: 0.354 AC: 14685 AN: 41438

American (AMR) AF: 0.215 AC: 3279 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3472

East Asian (EAS) AF: 0.0663 AC: 343 AN: 5176

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4808

European-Finnish (FIN) AF: 0.265 AC: 2802 AN: 10582

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18383 AN: 67928

Other (OTH) AF: 0.281 AC: 593 AN: 2110

Alfa AF: 0.275 Hom.: 27132

Bravo AF: 0.279

Asia WGS AF: 0.181 AC: 631 AN: 3478

EpiCase AF: 0.274

EpiControl AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.039
DANN	Benign	0.54
PhyloP100		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10493565; hg19: chr1-75699771; COSMIC: COSV63760233;